PROJECT ABSTRACT The nature and challenge of illicit drug use in the United States continues to change rapidly, evolving in reaction to myriad social, economic, and local forces. While drug addiction affects every region of the country, most information about drug use comes from large urban areas. Emerging data on rural addiction and its harms justify greater attention. Record drug use, addiction, and overdose rates in rural states, coupled with a dearth of treatment facilities, point to a rapidly worsening health situation. While health sciences have made considerable progress in understanding the etiology of drug use and uncovering the link between drug use and its many associated harms, this promising scientific news has yet to translate to better rural health outcomes. The goal of this application is to create a sustainable, nationally recognized Center?the Rural Drug Addition Research Center (RDAR)?dedicated to understanding the causes and impacts of rural drug addiction and its related challenges and harms. Given the multifactorial nature of addiction, this research must unfold across a continuum of domains, ranging from the microscopic level of the synapse to larger social contexts. As such, RDAR will draw on senior investigators and existing resources from the University of Nebraska to mentor early career scientists in conducting cutting-edge research that addresses rural drug use challenges from multiple angles (i.e., from synapse to society). For example, initial research projects will focus on the neuroscience of addiction, cognitive implications of chronic drug use, the relationship between rural drug use and violence exposure, and spatial and structural simulation of drug-related disease epidemiology. To support these projects, RDAR will found the Longitudinal Networks Core (LNC), a research core built around cutting-edge cohort tracking and retention software developed by RDAR senior investigators to offer longitudinal cohort study capacity to RDAR projects. LNC will recruit and retain a cohort of rural drug users from which RDAR projects will regularly collect data. The Center will provide dedicated mentoring, professional development, and Center resources to enable early stage investigators engaged in rural drug addiction research to become independently funded researchers (Aim 1) while creating a sustainable environment for interdisciplinary research excellence on rural illicit drug use and its harms (Aim 2). This will lay the groundwork for long-term Center infrastructure (Aim 3) that allows RDAR researchers to lead efforts to address specific challenges raised by drug addiction in rural settings and develop appropriate interventions for those settings. RDAR will combine the resources of a nationally recognized research university (University of Nebraska-Lincoln) and a university-based medical center (University of Nebraska Medical Center) to create a sustainable research environment, capitalizing on existing collaborations with local practitioners and state policy and service organizations. Lastly, institutional support in the form of pilot project funding and new faculty hires in research areas important to RDAR will help ensure the long-term sustainability of the Center.